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Preliminary preclinical study of Chol-DsiRNA polyplexes formed with PLL[30]-PEG[5K] for the RNAi-based therapy of breast cancer.
Ye, Zhen; Abdelmoaty, Mai Mohamed; Ambardekar, Vishakha V; Curran, Stephen M; Dyavar, Shetty Ravi; Arnold, Lora L; Cohen, Samuel M; Kumar, Devendra; Alnouti, Yazen; Coulter, Don W; Singh, Rakesh K; Vetro, Joseph A.
Afiliação
  • Ye Z; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA.
  • Abdelmoaty MM; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA; Therapeutic Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, Giza, Egypt.
  • Ambardekar VV; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA.
  • Curran SM; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA.
  • Dyavar SR; Department of Pharmacy Practice, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA.
  • Arnold LL; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
  • Cohen SM; Havlik-Wall Professor of Oncology, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
  • Kumar D; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA.
  • Alnouti Y; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA.
  • Coulter DW; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Department of Radiation Oncology, J. Bruce Henriksen Cancer Research Laboratories, University of Nebraska Medical Center, Omaha, NE, USA.
  • Singh RK; Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA.
  • Vetro JA; Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: jvetro@unmc.edu.
Nanomedicine ; 33: 102363, 2021 04.
Article em En | MEDLINE | ID: mdl-33545405
ABSTRACT
RNA interference molecules have tremendous potential for cancer therapy but are limited by insufficient potency after i.v. administration. We previously found that Chol-DsiRNA polyplexes formed between cholesterol-modified dicer-substrate siRNA (Chol-DsiRNA) and the cationic diblock copolymer PLL[30]-PEG[5K] greatly increase the activity of Chol-DsiRNA against a stably expressed reporter mRNA in primary murine syngeneic breast tumors after daily i.v. dosing. Here, we provide a more thorough preliminary preclinical study of Chol-DsiRNA polyplexes against the therapeutically relevant target protein, STAT3. We found that Chol-DsiSTAT3 polyplexes greatly increase plasma exposure, distribution, potency, and therapeutic activity of Chol-DsiSTAT3 in primary murine syngeneic 4T1 breast tumors after i.v. administration. Furthermore, inactive Chol-DsiCTRL polyplexes are well tolerated by healthy female BALB/c mice after chronic i.v. administration at 50 mg Chol-DsiCTRL/kg over 28 days. Thus, Chol-DsiRNA polyplexes may be a good candidate for Phase I clinical trials to improve the treatment of breast cancer and other solid tumors.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Polietilenoglicóis / Polilisina / Neoplasias da Mama / RNA Interferente Pequeno / Ribonuclease III / RNA Helicases DEAD-box / Terapêutica com RNAi Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Polietilenoglicóis / Polilisina / Neoplasias da Mama / RNA Interferente Pequeno / Ribonuclease III / RNA Helicases DEAD-box / Terapêutica com RNAi Idioma: En Ano de publicação: 2021 Tipo de documento: Article